2026-07-17T12:20:38Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/119182026-07-17T00:05:28Zcom_10259_11209com_10259_5086com_10259_2604col_10259_11210

Casajús, Ana 5554dd08-baae-4806-be57-3be03ae403b2 500 Zubiaur, Pablo e32e4997-27e8-492f-b14a-9a7c7fe226a9 500 Alday, Enrique 7a3434f6-5243-4ec6-b23e-30c07a25787b 500 Soria‐Chacartegui, Paula 914dbf20-d72b-4559-94fd-72d4c729773e 500 Saiz‐Rodríguez, Miriam a629585d-1214-4219-b144-d4eca623b896 500 Gutierrez, Lara b4b2a885-8c9b-40cb-a33e-348ac4956804 500 Aragonés, Catalina 32e135d3-bcab-46c1-93ce-fc54cc7d0449 500 Campodónico, Diana c4559759-efc4-478c-934a-5eb56398cd3c 500 Gómez‐Fernández, Antía 2412dd0c-4d3a-4fd2-8686-fbfc6eb98023 500 Navares‐Gómez, Marcos 64eb0afe-0b6b-41e8-bbeb-c882b917735f 500 Villapalos‐García, Gonzalo e7327f45-83f3-4c70-b99d-c409289f14cd 500 Mejía‐Abril, Gina 8801092d-2e0c-4920-a40e-6acf28cf79af 500 Ochoa, Dolores 45f30eef-93e1-4b1c-bb85-2814c3e783fa 500 Abad‐Santos, Francisco 788d0f1b-77ee-4bb0-ab59-203c90c38a44 500 2026-07-16T11:04:00Z 2026-07-16T11:04:00Z 2024-01 1752-8054 https://hdl.handle.net/10259/11918 10.1111/cts.13698 1752-8062 Tramadol is an important minor opioid prescribed for pain management. In this study, we analyzed the well-known impact of CYP2D6 genetic variation and 60 additional variants in eight candidate genes (i.e., ABCG2, SLCO1B1, CYP2D6, CYP2B6, CYP2C19, CYP2C9, CYP3A5, and CYP3A4) on tramadol efficacy and safety. Some 108 patients with pain after surgery admitted to a post-anesthesia care unit (PACU) and prescribed tramadol were recruited. They were genotyped, and tramadol M1/M2 metabolite concentrations were determined by a newly validated HPLC-MS/MS method. CYP2D6 intermediate (IM) and poor (PM) metabolizers showed lower M1 concentrations adjusted for dose/weight at 30 and 120 min compared to ultrarapid (UM) and normal (NM) metabolizers (univariate p < 0.001 and 0.020, multivariate p < 0.001 and 0.001, unstandardized β coefficients = 0.386 and 0.346, R2 = 0.146 and 0.120, respectively). CYP2B6 PMs (n = 10) were significantly related to a higher reduction in pain 30 min after tramadol intake (univariate p = 0.038, multivariate p = 0.016, unstandardized β coefficient = 0.224, R2 = 0.178), to lower PACU admission time (p = 0.007), and to lower incidence of adverse drug reactions (p = 0.038) compared to the other phenotypes. CYP3A4 IMs and PMs showed a higher prevalence of drowsiness and dizziness (p = 0.028 and 0.005, respectively). Our results suggest that the interaction of CYP2B6 and CYP2D6 phenotypes may be clinically relevant, pending validation of these results in large, independent cohorts. Additional research is required to clarify the impact of CYP3A4 genetic variation on tramadol response. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THIS TOPIC? Nowadays, CYP2D6 is considered the only clinically relevant pharmacogenetic biomarker for tramadol prescription; however, polymorphism of other metabolizing enzymes may be clinically relevant. WHAT QUESTION DID THIS STUDY ADDRESS? In this work, CYP2B6 genotype-informed phenotype was related to the response and tolerability to tramadol in patients with acute post-surgical pain. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? CYP2B6 phenotype may be more relevant than previously thought in relation to tramadol prescription; our results suggest that the interaction of CYP2B6 and CYP2D6 phenotypes may be clinically relevant, pending validation of these results in large, independent cohorts. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? CYP2D6 was the main predictor of tramadol M1 metabolite concentrations but had a modest impact on drug effectiveness and safety. P.S.-C. is financed by Universidad Autónoma de Madrid (FPI-UAM, 2021). G.V.-G. is co-financed by Instituto de Salud Carlos III (ISCIII) and the European Social Fund “Investing in Your Future” (PFIS predoctoral grant, number FI20/00090). M.N.-G. is financed by the ICI20/00131 grant, Acción Estratégica en Salud 2017–2020, ISCIII. P.Z. is financed by Universidad Autónoma de Madrid, Margarita Salas contract, grants for the requalification of the Spanish university system. M.S.-R. contract was supported by Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation, through the Sara Borrell Program (CD21/00022). eng ASCPT Clinical and Translational Science. 2024, V. 17, n. 1, art. 13698 https://doi.org/10.1111/cts.13698 Atribución-NoComercial 4.0 Internacional http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess Farmacogenómica Pharmacogenomics Tramadol Impact of CYP2D6 and CYP2B6 phenotypes on the response to tramadol in patients with acute post‐surgical pain info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Clinical and Translational Science 17 1 THUMBNAIL Casajus-CTS_2024.pdf.jpg Casajus-CTS_2024.pdf.jpg IM Thumbnail image/jpeg 4971 https://riubu.ubu.es/bitstream/10259/11918/4/Casajus-CTS_2024.pdf.jpg 717236ad86df21ae6104c3e67db43813 MD5 4 LICENSE license.txt license.txt text/plain; charset=utf-8 1362 https://riubu.ubu.es/bitstream/10259/11918/3/license.txt 5d013bfa6e473ff0db22cd82a4d71a70 MD5 3 CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 914 https://riubu.ubu.es/bitstream/10259/11918/2/license_rdf 24013099e9e6abb1575dc6ce0855efd5 MD5 2 ORIGINAL Casajus-CTS_2024.pdf Casajus-CTS_2024.pdf application/pdf 920804 https://riubu.ubu.es/bitstream/10259/11918/1/Casajus-CTS_2024.pdf f79d78fe7c9243741f01bc681eef9700 MD5 1 10259/11918 oai:riubu.ubu.es:10259/11918 2026-07-17 02:05:28.844 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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